Background: Necrotising enterocolitis (NEC) and sepsis are important causes of death and morbidity in preterm infants.
Administration of commensal bacteria to modify the bowel flora may strengthen intestinal barrier function and
prevent NEC and some cases of severe sepsis. Meta-analysis of over 20 published trials of probiotics
(1) suggests that probiotics prevent NEC and death, however use is limited. This may be because of lack of robust design
and concern about the generalisability of some of the trials (2).
The aim of the PiPS trial was to test a single bacterial strain probiotic product,
Bifidobacterium breve BBG-001 to
reduce NEC, sepsis and death in an unselected population of preterm babies large enough to give clear results.

Methods: The trial was funded by the NIHR through the Health Technology Assessment (HTA) and approved by South
Central Oxford A Research Ethics Committee and performed to ICH-GCP. PiPS is a multi-centre double blind
randomised placebo controlled trial of Bifidobacterium breve BBG-001, 2.1 to 5.3 x 108 CFU daily in infants
below 31 weeks of gestation, randomised within 48 hours of birth. Colonisation with
B breve was monitored by
culture and PCR of stools at 2w postnatal and 36w postmenstrual age. Primary outcomes were: NEC ≥Bell
stage 2, late onset sepsis and death. Results are presented by intention to treat adjusted for sex, gestation,
randomisation within 24 hours and allowing for clustering of multiples.

Analyses of the primary outcomes by subgroups defined by gestational age and birthweight were not suggestive
of differential effects in more mature babies and analysis of subgroups defined by colonisation status did not
suggest that efficacy was impacted by cross colonisation. Nor were there any differences in a range of clinical
and microbiological secondary outcomes.

Conclusion: This probiotic intervention shows no evidence of benefit in this population. This result supports the view that
different probiotic strains should be assessed separately and challenges the validity of combining trials using
different interventions in meta-analyses.